The Program in Radiation Biology is focused on ways in which the effectiveness of radiotherapy can increase local tumor control and survival of cancer patients. Three different approaches are being pursued to achieve this goal: 1) Development of pharmacologic and biologic agents to combine with radiotherapy and chemotherapy to improve local tumor control and prevent metastatic spread. 2) Development of new approaches and clinical trials to administer radiotherapy. 3) The identification of genetic determinants that influence the tumor response to radiation or the combination of chemotherapy and radiation using yeast and mammalian genetics. The research of program members has resulted in a series of important findings that include the regulation of stem cell differentiation by hypoxia, identifying a serum biomarker for tumor hypoxia, developing hypoxic specific cytotoxins for cancer therapy, identifying new genes that are essential for DNA repair and adaptation to stress, defining the role of p53 in global genomic DNA repair, generation of mouse models to dissect the role of p53 transactivation and p53 target genes in in vivo stress responses, the use of radiosurgery to treat pancreatic cancer, liver, lung and prostate cancer, and developing molecular and functional imaging techniques to direct the delivery of radiotherapy. The 23 program members representing the School of Medicine and Department of Biological Sciences in the School of Humanities and Sciences are highly motivated to develop new targeted therapeutics to combine with radiotherapy and are well supported by two program project grants and $4.3 million in NCI funding. During the last five years, the program members published 188 papers. With the support of the Cancer Center, the role of Radiation Biology in tumor immunity, stem cell recruitment and differentiation, and functional imaging will be further developed and expanded. In particular, the Cancer Center will greatly aid in translating many of the laboratorybased findings to increase the effectiveness of radiotherapy into the clinic.